title: A Recombinant Adenovirus Encoding Multiple HIV-1 Epitopes Induces Stronger CD4+T cell Responses than a DNA Vaccine in Mice.
abstract: T-cell based vaccines against SIV/HIV may reduce both transmission and disease progression by inducing broad and functionally relevant T cell responses. Mounting evidence points toward a critical role for CD4+T cells in the control of immunodeficiency and virus replication. We have previously shown that a DNA vaccine (HIVBr18), encoding 18 HIV CD4 epitopes capable of binding to multiple HLA class II molecules was able to elicit broad, polyfunctional, and long-lived CD4+and CD8+T cell responses in BALB/c and multiple HLA class II transgenic mice. By virtue of inducing broad responses against conserved CD4+T cell epitopes that could be recognized across diverse common HLA class II alleles, this vaccine concept may cope with HIV-1 genetic variability and increase population coverage. Given the low immunogenicity of DNA vaccines in clinical trials, we tested the ability of a recombinant adenovirus serotype 5 encoding the 18 HIV epitopes (Ad5-HIVBr18) to increase specific cellular immune responses. We assessed the breadth and magnitude of HIV-specific proliferative and cytokine responses of CD4+and CD8+T cells induced by Ad5-HIVBr18 using different vaccination regimens/routes and compared to DNA immunization. Immunization with Ad5-HIVBr18 induced significantly higher specific CD4+and CD8+T cell proliferation, IFN-γ and TNF-α production than HIVBr18. The subcutaneous route of Ad5-HIVBr18 administration was associated with the highest responses. Ad5-HIVBr18 induced higher proliferative and cytokine responses than HIVBr18 up to 28 weeks post-immunization. Our results indicate that a vaccine based on an adenovirus vector encoding the HIVBr18 epitopes shows superior immunogenicity as compared to its DNA counterpart. These results support the possible testing of a vaccine encoding HIVBr18 in non-human primates and future clinical trials.
authors.affiliation: Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and Allergy, Department of Medicine, Brazil ; Institute for Investigation in Immunology-INCT, Sao Paulo, Brazil ; Division of Immunology-Federal University of Sao Paulo-UNIFESP, Sao Paulo, Brazil.
authors.forename: Daniela Santoro
authors.initials: DS
authors.lastname: Rosa
authors.forename: Susan Pereira
authors.initials: SP
authors.lastname: Ribeiro
authors.forename: Rafael Ribeiro
authors.initials: RR
authors.lastname: Almeida
authors.forename: Eliane Conti
authors.initials: EC
authors.lastname: Mairena
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
keywords: Adenovirus; CD4+ T cells; Epitopes; HIV vaccine; HIV-1; Polyfunctional; Vaccine